The objectives of this project are to develop a method for investigating the nature of splenic microcirculation, to understand how the splenic microcirculation is altered under pathological conditions, and to study the regulation of microcirculation and hematopoiesis in the cultured mouse embryo. The method for studying the splenic microcirculation involves (a) injection of plastic microspheres of suitable size into the blood stream, (b) termination of the blood flow upon the arrival of the microspheres in the spleen, and (c) preparation of the histological sections of the splenic tissue for studying the microsphere distribution in the spleen. The relative blood flow to the closed and open circulation in the spleen is determined by enumerating the microspheres within and without the splenic sinuses. This microsphere method can be used to study possible alterations in the microcirculation of the spleen from rats with acute malaria infection. For the study of microcirculation and hematopoiesis in the mouse embryo, the embryos are cultured from the blastocyst stage to the early somite stage under various culture conditions. The hematopoiesis and microvasculature in the yolk sac of the cultured mouse embryo are studied by light and electron microscopy.